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Журнал «Медицина неотложных состояний» Том 21, №6, 2025

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Три контури захисту мітохондрій при гострому панкреатиті: біоенергетика, редокс-баланс і блокада пори перехідної проникності

Три контури захисту мітохондрій при гострому панкреатиті: біоенергетика, редокс-баланс і блокада пори перехідної проникності

Авторы: Чуклін С.М., Чуклін С.С.
Медичний центр Святої Параскеви, м. Львів, Україна

Рубрики: Медицина неотложных состояний

Разделы: Справочник специалиста

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Резюме

Мітохондріальна дисфункція є ключовою патогенетичною ланкою гострого панкреатиту (ГП), спричиняючи порушення вироблення АТФ, втрату мембранного потенціалу (m), утворення активних форм кисню (АФК) та відкриття пори перехідної проникності (mPTP), що призводить до некрозу ацинарних клітин і системної запальної відповіді. Це обґрунтовує доцільність терапевтичного втручання, спрямованого на стабілізацію мітохондріального гомеостазу. Мета: систематизувати сучасні експериментальні підходи до мітохондріально-спрямованої терапії при ГП, зосереджені на трьох напрямках: підтримці мітохондріального біоенергетичного гомеостазу, антиоксидантній дії та інгібуванні відкриття mPTP. Проведено аналіз оригінальних досліджень із баз даних PubMed, Scopus і Google Scholar, присвячених впливу фармакологічних агентів на функцію мітохондрій в експериментальних моделях ГП. Оцінювалися біоенергетичні параметри (синтез АТФ, m), рівні окисного стресу, активація сигнальних шляхів (SIRT1, Nrf2, HtrA2, PGC-1), ступінь некрозу, інтенсивність запальної відповіді й активність mPTP. Засоби, що підтримують енергетичну функцію мітохондрій (карнітин, NMN, еламіпретид, коензим Q10, мелатонін), сприяють збереженню m, стимуляції ЦТК та поліпшенню виживання клітин. Антиоксиданти (куркумін, гідрокситирозол, кверцетин, астрагалозид IV, тирон) демонструють здатність зменшувати АФК-залежне ушкодження, активуючи внутрішньоклітинні шляхи Nrf2/ARE. Інгібітори mPTP (циклоспорин, SS-31) запобігають відкриттю пори, зменшуючи втрату m і некроз. MitoTEMPO і HRS діють насамперед як таргетні антиоксиданти, знижуючи рівень мтАФК, що, як наслідок, супроводжується пригніченням інфламасомної активації. Водночас деякі агенти (MitoQ, SkQ1) давали несприятливі ефекти або погіршення перебігу. Мітохондріальна таргетна терапія є перспективним напрямом експериментального лікування ГП. Засоби, які відновлюють біоенергетичну функцію, зменшують оксидативний стрес і блокують відкриття mPTP, забезпечують морфофункціональний захист ацинарних клітин. Подальші дослідження мають бути спрямовані на клінічну апробацію найефективніших агентів та оптимізацію комбінованих підходів.

Mitochondrial dysfunction plays a central role in the pathogenesis of acute pancreatitis (AP), leading to impaired adenosine triphosphate (ATP) production, loss of mitochondrial membrane potential (m), excessive reactive oxygen species (ROS) formation, and opening of the mitochondrial permeability transition pore (mPTP), which drives acinar cell necrosis and systemic inflammation. These mechanisms highlight mitochondria as a promising therapeutic target. The purpose was to summarize experimental strategies for mitochondria-targeted therapy in AP, focusing on three major aspects: support of bioenergetic homeostasis, antioxidant action, and inhibition of mPTP ope­ning. A structured analysis of original experimental studies from PubMed, Scopus, and Google Scholar was conducted. Studies examined the effects of mitochondria-targeted agents on ATP synthesis, m stabilization, oxidative stress, regulatory pathways (SIRT1, Nrf2, HtrA2, PGC-1), necrosis, inflammatory response, and mPTP regulation in AP models. Energy-supporting agents (e.g., carnitine, NMN, elamipretide, coenzyme Q10, melatonin) enhanced mitochondrial function and acinar cell viability. Antioxidants (e.g., curcumin, hydroxytyrosol, quercetin, astragaloside IV, tiron) reduced ROS-mediated injury via Nrf2/ARE pathway activation. mPTP inhibitors (cyclosporine, SS-31) preserved m and reduced necrosis. MitoTEMPO and hydrogen-rich saline primarily acted as mitochondria-targeted antioxidants, reducing ROS levels, which secondarily resulted in suppression of inflammasome activation. In contrast, MitoQ and SkQ1 showed unfavorable or inconsistent results. Mitochondria-targeted therapy is a promising approach to experimental AP treatment. Agents that support mitochondrial energetics, reduce oxidative stress, and inhibit mPTP opening offer cytoprotective benefits and may improve disease outcomes. Future research should focus on clinical validation and combined therapeutic strategies.


Ключевые слова

гострий панкреатит; мітохондріальна дисфункція; мітохондріальна таргетна терапія; огляд

acute pancreatitis; mitochondrial dysfunction; mitochondrial targeted therapy; review

doi: http://dx.doi.org/10.22141/2224-0586.21.6.2025.1943

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